Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31

Abstract

We report a clinical and genetic study of a French family among whom febrile convulsions (FC) are associated with subsequent temporal lobe epilepsy (TLE) in the same individual, without magnetic resonance imaging-identifiable hippocampal abnormalities. Linkage analyses excluded the loci FEB1 and FEB2, previously implicated in FC; the GEFS+1 locus responsible for generalized epilepsy with febrile seizures plus; and the locus implicated in lateral temporal lobe epilepsy. After scanning the entire genome, significant lod scores (>3) for markers on 18qter and suggestive lod scores (>2) for markers on 1q25-q31 were obtained. An analysis of the haplotypes at these two loci supported the hypothesis that two genes segregated with the phenotype. All patients shared common haplotypes for both 1q25-q31 and 18qter chromosomes. All but one unaffected at-risk individuals carried only one, or none, of the disease haplotypes. Under the assumption of digenic inheritance, haplotype reconstruction defined a 26 cM interval on chromosome 1 and a 10 cM interval on chromosome 18. This family suggests that the association between FC and TLE may be observed in the absence of hippocampal structural abnormalities and that they may have, in some cases, a common genetic basis.

Chromosome 18 aberrations and epilepsy: A review

“…In most patients, seizures appear to be focal, mainly occurring during the first years of life and well controllable. Interestingly, in agreement with these data, Baulac et al [2001] reported a French family presenting with temporal lobe epilepsy and febrile convulsions, in whom a genome-wide scan demonstrated evidence for markers at 18qter.…”

Association Analysis of γ2 Subunit of γ-Aminobutyric Acid Type A Receptor Polymorphisms with Febrile Seizures

“…The gene for generalized epilepsy with FS plus, which is an epileptic syndrome characterized by FSs persisting beyond age 6 y and non-FSs, was identified as SCN1B, the gene coding for the accessory subunit ␤1 of the voltage-gated sodium channel (5,6). Digenic inheritance was suggested for pedigree segregating FSs and temporal lobe epilepsy and loci mapped to chromosome 1q and 18qter (32).…”

Under What Circumstances Can Seizures Produce Hippocampal Injury: Evidence for Age-Specific Effects

“…FTLE may be associated with febrile seizures [104][105][106][107][108] or MTS [108,109]. FTLE associated with febrile seizures has been linked to sodium channel SCN1A mutations [104].…”